Predictions of Pathological Features and Recurrence Based on FDG-PET Findings of Esophageal Squamous Cell Carcinoma after Trimodal Therapy.

BACKGROUND: The degree of metabolic activity in tumor cells can be determined by 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET). Associations between FDG uptake by primary tumors of locally advanced esophageal squamous cell carcinoma (ESCC) under trimodal therapy and the pathological features of such tumors have not been fully investigated. PATIENTS AND METHODS: We evaluated relationships between the maximal standardized uptake (SUVmax) in primary tumors on preoperative PET images and pathological features as well as cancer recurrence in 143 patients with ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) followed by surgery. RESULTS: The post-SUVmax significantly differed after NCRT for ypT and ypN status, lymphatic invasion (LI), venous invasion (VI), and recurrence. Furthermore, the %ΔSUVmax (rate of decrease between before and after NCRT) for LI, VI, and recurrence significantly differed. Univariate and multivariate analyses selected post-SUVmax and %ΔSUVmax as independent preoperative predictors of recurrence-free survival [hazard ratio (HR) 1.46; 95% confidence interval (CI) 1.24-1.72 and HR 0.97; 95% CI 0.96-0.99, respectively; p < 0.001 for both]. Recurrence-free and overall survival were significantly stratified according to optimal SUVmax cutoffs for predicting recurrence (post- and %ΔSUVmax: 2.8 and 70, respectively). CONCLUSIONS: The post- and %ΔSUVmax of primary tumors were significantly associated with the pathological features and recurrence of ESCC under trimodal therapy. Therefore, FDG-PET can preoperatively predict the degree of aggressive tumor behavior in ESCC under trimodal therapy.

Clinical Significance of 18F-Fluorodeoxyglucose-Positron Emission Tomography-Positive Lymph Nodes to Outcomes of Trimodal Therapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND: The clinical significance of lymph node (LN) status determined by preoperative 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) has not been investigated in patients with locally advanced esophageal squamous cell carcinoma (ESCC) treated with neoadjuvant chemoradiotherapy (NCRT) followed by surgery (trimodal therapy). METHODS: This study reviewed 132 consecutive patients with ESCC who had been preoperatively evaluated using FDG-PET before and after NCRT to analyze associations among LN status according to PET findings, pathologic LN metastasis, and prognosis of ESCC after trimodal therapy. RESULTS: Lymph nodes that were PET-positive both before and after NCRT comprised significant predictive markers of pathologic LN metastasis in station-by-station analyses (sensitivity, specificity, and accuracy respectively 41.7%, 95.0%, and 92.7% before, and 12.0%, 99.4%, and 95.6% after NCRT; both p < 0.0001). The numbers of LNs evaluated using PET before and after NCRT were significantly associated with those of pathologic metastatic LNs. Uni- and multivariable analyses selected LN status determined by PET before NCRT as a significant independent predictor of both recurrence-free [LN-negative vs LN-positive: hazard ratio (HR) 1.90; 95% confidence interval (CI) 1.02-3.23; p = 0.045] and overall survival (HR 2.62; 95% CI 1.29-5.30; p = 0.01). CONCLUSIONS: The status of LN determined by preoperative FDG-PET is significantly associated with pathologic LN status and the prognosis of ESCC with trimodal therapy. Thus, FDG-PET is a useful diagnostic tool for preoperative prediction of pathologic LN metastasis and survival among patients with ESCC.

Treatment Outcomes and Prognostic Factors After Recurrence of Esophageal Squamous Cell carcinoma.

BACKGROUND: The evaluation of treatment outcomes and detection of prognostic factors after recurrence are very important for tailoring optimal therapies for individual patients with recurrent esophageal cancer. METHODS: We reviewed 133 patients in whom esophageal squamous cell carcinoma (ESCC) recurred after curative surgery, and assessed recurrence patterns, treatment outcomes and prognostic factors. RESULTS: Recurrence in 57 (42.9%), 54 (40.6%) and 22 (16.5%) patients was locoregional, distant and combined, respectively. The median amounts of elapsed time until recurrence and median survival after recurrence for all patients were 9.1 and 8.3 months, respectively. Univariate and multivariate analyses selected time to recurrence (hazard ratio [HR], 0.98; 95% confidence interval [CI], 0.97-0.999; p = 0.04), recurrence location (locoregional vs. distant: HR, 1.63; 95% CI, 1.03-2.61; p = 0.04), number of organs with recurrence (1 vs. 3: HR, 3.49; 95% CI, 1.23-9.87; p = 0.02) and treatment after recurrence (best supportive care, [BSC] vs. chemotherapy [CT] or radiation therapy [RT]: HR, 0.37; 95% CI, 0.15-0.94; p = 0.04; BSC vs. CT and RT: HR, 0.50; 95% CI, 0.26-0.94; p = 0.03; BSC vs. surgery: HR, 0.47; 95% CI, 0.25-0.88; p = 0.02) as independent factors for survival after recurrence. Seventeen (12.8%) patients who had localized lymph node recurrence and lung oligometastasis and received multidisciplinary therapy after recurrence survived for >3 years thereafter. CONCLUSION: Despite the poor survival of patients with ESCC and early or distant recurrence or recurrence in ≥3 recurrent organs, appropriate multimodal therapies should be tailored for individual patients with recurrent ESCC.

Evaluation of Prognostic Factors for Esophageal Squamous Cell Carcinoma Treated with Neoadjuvant Chemoradiotherapy Followed by Surgery.

BACKGROUND: Intensive trimodality therapy is needed for locally advanced esophageal squamous cell carcinoma (ESCC). However, some patients develop recurrence and die of cancer even after trimodality therapy. METHODS: We evaluated prognostic factors based on data from 125 patients with ESCC who underwent neoadjuvant chemoradiotherapy (NCRT) comprising concurrent chemotherapy and 40 Gy of radiation, followed by curative-intent esophagectomy. RESULTS: Thirty-four (27.2%) patients achieved a pathological complete response (pCR) after NCRT. The 5-year recurrence-free (RFS) and overall survival (OS) rates of all patients were 49.2 and 52.9%, respectively, and were significantly better for patients with pCR than without pCR (p = 0.01 and 0.02, respectively). Univariate and multivariate analyses selected performance status [PS 0 vs. 1: hazard ratio (HR) 2.05; 95% confidence interval (CI) 1.30-4.84; p = 0.01] and ypN (0 vs. 1: HR 2.33; 95% CI 1.12-4.84; p = 0.02; 0 vs. 2/3: HR 3.73; 95% CI 1.68-8.28; p = 0.001) as independent covariates for RFS. Furthermore, PS (0 vs. 1; HR 2.94; 95% CI 1.51-5.72; p = 0.002) and ypN (0 vs. 1; HR 2.26; 95% CI 1.09-4.69; p = 0.03; 0 vs. 2/3: HR 3.90; 95% CI 1.79-8.48; p = 0.001) were also independent covariates for OS. CONCLUSIONS: Performance status 1 and ypN+ were significantly associated with a poor prognosis after trimodality therapy for ESCC.

Role of Postoperative C-Reactive Protein Levels in Predicting Prognosis After Surgical Treatment of Esophageal Cancer.

BACKGROUND: Elevated preoperative serum C-reactive protein (CRP) levels are reportedly associated with a poor prognosis for patients with various types of malignant tumors. However, the impact of postoperative CRP levels on the prognosis of patients with esophageal cancer remains unknown. The present study aims to clarify the prognostic significance of postoperative CRP levels on the survival of patients with esophageal cancer. METHODS: We reviewed the records of consecutive 202 patients with thoracic esophageal squamous cell carcinoma who underwent transthoracic esophagectomy. We measured serum CRP levels on postoperative days (PODs) 1, 2, 3, 5 and 7 and evaluated the relationships between postoperative CRP levels and survival. RESULTS: The findings of Cox regression analyses suggested that elevated CRP levels on POD 3, 5 and 7 were associated with poor recurrence-free survival (RFS). We divided CRP levels on POD 7 into three tertiles and found that RFS could be clearly stratified, being the poorest (p < 0.001) in the highest tertile (high CRP). The trend was similar even in patients with or without infectious complications and with or without advanced pathological stage. Multivariate analysis showed that pathologically advanced stage (Hazard ratio [HR], 5.14; 95% confidence interval [CI] 2.67-9.87; p < 0.001) and high CRP (HR, 2.27; 95% CI 1.3-3.96; p = 0.004) were independent predictors of RFS. CONCLUSION: Postoperative CRP levels could predict the prognosis of patients with esophageal cancer. We propose that the clinical course of postoperative CRP level should be carefully monitored as a predictor of survival.

Clinical Significance of FDG-PET to Predict Pathologic Tumor Invasion and Lymph Node Metastasis of Superficial Esophageal Squamous Cell Carcinoma.

PURPOSE: To determine the preoperative ability of [18F]-fluoro-2-deoxyglucose positron emission tomography (FDG-PET) to predict pathologic tumor invasion and lymph node status in cT1N0M0 esophageal squamous cell carcinoma (ESCC). METHODS: We retrospectively analyzed 40 consecutive patients diagnosed with cT1N0M0 ESCC between February 2006 and April 2011. All patients were treated by esophagectomy with two- or three-field lymphadenectomy without neoadjuvant therapy. We evaluated the relevance between clinical variables including maximum standardized uptake values (SUVmax) of the primary tumor on FDG-PET and pathologic tumor invasion and lymph node status using a logistic regression model. RESULTS: Tumors invaded the middle submucosal layer (SM2) and beyond in 21 (52.5 %) patients, and 6 (15 %) had lymph node metastases. The areas under receiver operating characteristic (ROC) curves for SUVmax of the primary tumor used to predict factors involved in tumor infiltration to SM2 or deeper and lymph node metastasis were 0.75 (p = 0.006) and 0.79 (p = 0.025), respectively. The optimal SUVmax cutoff was 2.7. The findings of univariate and multivariate analyses identified SUVmax as the only significant preoperative predictor associated with tumor infiltration into SM2 or beyond and lymph node metastasis. Furthermore, SUVmax ≥ 2.7 of the primary tumor on FDG-PET was associated with poor recurrence-free and disease-specific survival (p = 0.019 and p = 0.012, respectively). CONCLUSIONS: FDG-PET is helpful for diagnosing tumors that can infiltrate SM2 and beyond as well as occult lymph node metastasis of cT1N0M0 ESCC that are valuable indications in deciding therapeutic strategies for superficial ESCC.

Surgical Resection of Thoracic Esophageal Cancer with Interstitial Lung Disease: A Case Report.

Patients with esophageal cancer often have various comorbidities, and these sometimes limit treatment choices. We describe a patient with stage IA esophageal cancer accompanied by interstitial lung disease (ILD). Endoscopic resection and radiotherapy were not appropriate because of clinically diagnosed submucosal invasion and the patient was at high risk of ILD exacerbation. We therefore selected transhiatal esophagectomy without a thoracotomy considering the risk of postoperative respiratory complications, and administered methylprednisolone and sivelestat in the perioperative period for the reduction of surgical stress. To our knowledge, this is the first report of surgical treatment for esophageal cancer with ILD. The patient was discharged without postoperative complications. Transhiatal esophagectomy is an appropriate choice for patients with early-stage esophageal cancer without lymph node metastasis who are at high risk for postoperative respiratory complications. The appropriate selection of treatment is important for patients with esophageal cancer considering the risk of complications.

Association between [18F]-fluoro-2-deoxyglucose uptake and expressions of hypoxia-induced factor 1α and glucose transporter 1 in non-small cell lung cancer.

OBJECTIVE: High maximum standardized uptake values on [(18)F]-fluoro-2-deoxyglucose positron emission tomography are associated with inferior survival in non-small cell lung cancer. Here, we investigated the biological mechanisms underlying [(18)F]-fluoro-2-deoxyglucose uptake in non-small cell lung cancer. METHODS: This study included 133 patients with non-small cell lung cancer (109 with adenocarcinoma and 24 with squamous cell carcinoma). The patients underwent tumour resection, at the latest, 4 weeks after [(18)F]-fluoro-2-deoxyglucose positron emission tomography. The maximum standardized uptake values for primary lesions were calculated based on [(18)F]-fluoro-2-deoxyglucose uptake. The expression of hypoxia-inducible factor 1α and glucose transporter 1 was evaluated on immunostained tumour sections using six-point grading scales. RESULTS: Maximum standardized uptake values and the expression of hypoxia-inducible factor 1α and glucose transporter 1 were significantly higher in squamous cell carcinoma than in adenocarcinoma (P < 0.001, P = 0.034 and P < 0.001, respectively). In adenocarcinoma, but not squamous cell carcinoma, maximum standardized uptake values, hypoxia-inducible factor 1α and glucose transporter 1 correlated with various clinicopathological factors relating to malignancy, and maximum standardized uptake values and glucose transporter 1 were associated with disease-free survival (P < 0.001 and P = 0.029) and overall survival (P < 0.001 and P = 0.033, respectively). Patients with high expression of hypoxia-inducible factor 1α tended to exhibit shorter disease-free survival and overall survival than those with low expression, but the differences were not significant (P = 0.32 and P = 0.15, respectively). And then in adenocarcinoma, hypoxia-inducible factor 1α and glucose transporter 1, glucose transporter 1 and maximum standardized uptake values, and hypoxia-inducible factor 1α and maximum standardized uptake values were significantly correlated (P < 0.001 for all), suggesting that hypoxia-inducible factor 1α-induced glucose transporter 1 might influence maximum standardized uptake values on [(18)F]-fluoro-2-deoxyglucose positron emission tomography. CONCLUSIONS: In lung adenocarcinoma, but not squamous cell carcinoma, hypoxia-inducible factor 1α and glucose transporter 1 expressions indicate tumour aggressiveness pathologically and might explain high [(18)F]-fluoro-2-deoxyglucose uptake on positron emission tomography and correlate with poor prognosis.

Laparoscopic Repair and Percutaneous Endoscopic Gastrostomy to Treat Giant Esophageal Hiatal Hernia with Gastric Obstruction: A Case Report.

We describe a 74-year-old man with repeated aspiration pneumonia who developed gastric obstruction due to giant esophageal hiatal hernia (EHH). We repaired the giant EHH by laparoscopic surgery and subsequently anchored the stomach to the abdominal wall by percutaneous endoscopic gastrostomy (PEG) using gastrofiberscopy. Thereafter, the patient resumed oral intake and was discharged on postoperative day 21. At two years after these procedures, the patient has adequate oral intake and lives at home. Because this condition occurs more frequently in the elderly with comorbidities, laparoscopic surgery contributes to minimally invasive treatment. Furthermore, the procedure combined with concurrent gastropexy via PEG is useful for treating patients who have difficulty swallowing and for preventing recurrent hernia.

Follicular lymphoma without lymphadenopathy incidentally diagnosed by sentinel lymph node biopsy during breast cancer surgery: a case report.

BACKGROUND: Concurrent breast cancer and malignant lymphoma is a rare phenomenon. This report describes malignant lymphoma that was incidentally diagnosed from a sentinel lymph node biopsy (SLNB) during breast cancer surgery. CASE PRESENTATION: A 73-year-old woman with a history of ovarian cancer and diabetes presented with right focal asymmetric density on a mammogram acquired during routine breast cancer screening. Ultrasonography (US) and magnetic resonance imaging (MRI) showed a 13.5-mm tumor in the upper lateral region of the right breast. A US-guided Mammotome biopsy revealed invasive ductal carcinoma of the right breast. Preoperative assessments including positron emission tomography-computerized tomography, found no evidence of axillary lymphadenopathy or distant metastasis. Because the breast cancer was stage I, the patient underwent a right mastectomy and a sentinel lymph node biopsy (SLNB) at our hospital. Pathological assessment of the biopsy revealed follicular lymphoma (FL), but no metastatic breast cancer. The patient was referred to hematology to stage the FL. Bone marrow findings were negative and stage I FL was diagnosed. After the mastectomy, she was monitored and given adjuvant therapy with an aromatase inhibitor. CONCLUSIONS: Follicular lymphoma was incidentally diagnosed from an SLNB obtained to determine the dissemination of early-stage breast cancer. Collaboration with hematologists is important to determine optimal treatment plans for such patients regardless of the rarity of such events.

Early Recurrence and Cancer Death After Trimodal Therapy for Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: Although locally advanced esophageal squamous cell carcinoma (ESCC) can be controlled and survival can be prolonged by neoadjuvant chemoradiotherapy (NCRT) followed by surgery (trimodal therapy), some patients still develop early recurrence and die of cancer even after such intensive therapy. The present study aimed to determine the factors associated with early recurrence and cancer death for patients with ESCC treated by trimodal therapy. PATIENTS AND METHODS: We evaluated risk factors for recurrence within 6 months, as well as cancer death within 1 year based on data from 141 patients with ESCC who underwent NCRT followed by curative esophagectomy. RESULTS: The carcinoembryonic antigen level before treatment, postoperative complications, pathology after neo-adjuvant therapy (ypT, ypN), lymphatic invasion, venous invasion and pathological response of the primary tumor were significant factors in a comparison of patients with and without early recurrence. Multivariate analysis subsequently selected ypN [ypN, 0/1 vs. 2/3; hazard ratio (HR)=4.13, 95% confidence interval (CI)=1.25-13.66; p=0.02] as an independent covariate for early recurrence. Postoperative complications, ypT, ypN, poorer tumor differentiation, lymphatic invasion and venous invasion were significant factors in a comparison of patients with and without early cancer death. Multivariate analysis subsequently selected postoperative complications of grade ≥3b (vs. <3b) defined according to the Clavien-Dindo classification (HR=5.9, 95% CI=1.53-23.47; p=0.01) and venous invasion (vs. without: HR=4.80, 95% CI=1.21-19.14; p=0.03) as independent covariates for early cancer death. CONCLUSION: Further reduction of postoperative complications are needed after NCRT for patients with ESCC. Meticulous surveillance and postoperative adjuvant therapy should be considered for patients with risk factors for early recurrence and cancer death.

Traditional Japanese herbal medicine rikkunshito increases food intake and plasma acylated ghrelin levels in patients with esophageal cancer treated by cisplatin-based chemotherapy.

BACKGROUND: Cisplatin (CDDP) is an important chemotherapeutic drug for treating esophageal cancer that often induces nausea and vomiting. Rikkunshito (RKT), a traditional Japanese herbal medicine, can increase levels of plasma ghrelin, which is an orexigenic gut hormone that can alleviate chemotherapy-induced nausea and vomiting (CINV) and anorexia. METHODS: This prospective randomized crossover study included 20 patients with esophageal cancer who were administered with CDDP-based chemotherapy. Ten of them were assigned to group A [1st course: with RKT 7.5 g/day on days 1-14; 2nd course: without RKT (control)] and 10 were assigned to group B [1st course: without RKT (control); 2nd course: with RKT 7.5 g/day on days 22-35]. Food intake and levels of plasma acylated ghrelin (AG) were compared between the control and RKT courses. RESULTS: Data from 18 patients were included in this analysis, as chemotherapy was immediately stopped due to deteriorating renal function in one patient and intracerebral bleeding in another. The median rate at which food intake decreased between days 4 and 6 was considerably lower in the course with, than without RKT (2% vs. 30%; P=0.02). Median levels of AG significantly increased from days 3 to 8 in patients in both courses with and without RKT (9.6 to 15.7 fmol/mL, P<0.0001; control, 10.2 to 17.8, P=0.0002). The rate at which median plasma AG levels increased from days 3 to 8 tend to be higher in the RKT, than in the control course (68% vs. 48%, P=0.08). CONCLUSIONS: RKT can improve CDDP-induced, delayed-onset anorexia and increase plasma AG levels among patients with esophageal cancer who undergo highly emetogenic chemotherapy (HEC).

Impact of Interval Between Neoadjuvant Chemoradiation and Surgery Upon Morbidity and Survival of Patients with Squamous Cell Carcinoma of Thoracic Esophagus.

BACKGROUND/AIM: The present study aimed to determine the effects of intervals between neoadjuvant chemoradiotherapy (nCRT) and esophagectomy on therapeutic outcomes in patients with locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: We analyzed data from 134 consecutive patients who were diagnosed with locally advanced ESCC of the thoracic esophagus and were treated by nCRT followed by esophagectomy between September 2003 and September 2015. We assigned the patients to groups A and B according to whether they underwent esophagectomy ≤8 or >8 weeks after nCRT. RESULTS: The two groups were comparable in terms of age, gender, performance status, comorbidities, tumor location, clinical stage, R0 resection rates and pathological responses to nCRT. The incidences of pneumonia and respiratory failure were significantly higher in group B (p=0.03, p=0.009, respectively). Recurrence-free (RFS) and overall (OS) survival rates did not significantly differ between the two groups. However, RFS was significantly poorer among patients with R0 resection (p=0.04) and those of cStages III and IV (p=0.009) in group B. CONCLUSION: Esophagectomy should proceed within eight weeks after nCRT from the viewpoints of respiratory morbidity and impact of RFS on patients with R0 resection.

Preoperative prediction of a pathologic complete response of esophageal squamous cell carcinoma to neoadjuvant chemoradiotherapy.

BACKGROUND: The accurate prediction of a pathologic complete response (ypT0N0M [LYM] 0 ypStage 0) before operation is essential for selecting appropriate strategies for treating esophageal cancer after neoadjuvant chemoradiotherapy. METHODS: We reviewed 130 consecutive patients with esophageal squamous cell carcinoma who were evaluated preoperatively using upper gastrointestinal endoscopy, computed tomography, and 18F-fluorodeoxyglucose-positron emission tomography after neoadjuvant chemoradiotherapy and subsequently underwent esophagectomy. Our aim was to determine the diagnostic abilities of computed tomography, 18F-fluorodeoxyglucose-positron emission tomography, and endoscopy to predict preoperatively a pathologic complete response of the primary site of the locally advanced esophageal squamous cell carcinoma and associated lymph nodes to trimodal neoadjuvant chemoradiotherapy. Associations between clinical complete response (ycT0N0M [LYM] 0 ycStage 0) and pathologic complete response were investigated preoperatively. RESULTS: Twenty-nine (22.3%) and 43 (33.1%) patients, respectively, achieved clinical complete response and pathologic complete response, which were associated (P=.001). The sensitivity and specificity, as well as the positive and negative predictive values of clinical complete response to define pathologic complete response were 39.5%, 86.2%, 58.6%, and 74.3%, respectively. Univariate and multivariate analyses selected clinical complete response as the sole independent preoperative predictor of pathologic complete response (clinical complete responses versus non-clinical complete responses: odds ratio: 0.26, 95% confidence interval, 0.10-0.65, P=.004). Recurrence-free and overall survival (OS) rates were better in patients with than in those without clinical complete response (5-year recurrence-free and overall survival: 69.0% vs 41.4% and 75.9% vs 45.0%, respectively, both P=.02). Furthermore, clinical complete response was an independent preoperative predictor of recurrence-free survival (clinical complete response versus nonclinical complete response: hazard ratio: 2.20, 95% confidence interval, 1.08-4.45, P=.03). CONCLUSION: Although pathologic complete response was predictable preoperatively to some extent, the accuracy was somewhat low. Considerable caution should be exercised when selecting the watch-and-wait approach with operation as needed and omitting planned operative intervention even for patients who achieve clinical complete response after neoadjuvant chemoradiotherapy.

Clinicopathologic Features of Submucosal Esophageal Squamous Cell Carcinoma.

BACKGROUND: The prognoses of submucosal esophageal squamous cell carcinoma patients vary. Patients with favorable prognoses may receive less invasive or nonsurgical interventions, whereas patients with poor prognoses or advanced esophageal cancer may require aggressive treatments. We sought to identify prognostic factors for patients with submucosal esophageal squamous cell carcinoma, focusing on lymph node metastasis and recurrence. METHODS: We included 137 submucosal esophageal squamous cell carcinoma patients who had undergone transthoracic esophagectomy with systematic extended lymph node dissection. Submucosal tumors were classified as SM1, SM2, and SM3 according to the depth of invasion. Prognostic factors were determined by univariable and multivariable analyses. RESULTS: Lymph node metastasis was observed in 18.8%, 30.5%, and 50.0% of SM1, SM2, and SM3 cases, respectively. The overall 5-year recurrence rate was 21.9%; the rates for SM1, SM2, and SM3 tumors were 9.4%, 18.6%, and 34.8%, respectively. The SM1 tumors all recurred locoregionally; distant metastasis occurred in SM2 and SM3 cases. The 5-year overall survival rates were 83%, 77%, and 59% for SM1, SM2, and SM3 cases, respectively. On univariable analysis, lymph node metastasis, depth of submucosal invasion (SM3 versus SM1/2), and tumor location (upper thoracic versus mid/lower thoracic) were poor prognostic factors for overall survival. Multivariable Cox regression analyses identified depth of submucosal invasion (hazard ratio 2.51, 95% confidence interval: 1.37 to 4.61) and tumor location (hazard ratio 2.43, 95% confidence interval: 1.18 to 4.63) as preoperative prognostic factors. CONCLUSIONS: Tumor location (upper thoracic) and infiltration (SM3) are the worse prognostic factors of submucosal esophageal squamous cell carcinoma, but lymph node metastasis is not a predictor of poorer prognosis.

Effects of Neoadjuvant Chemoradiotherapy on Pathological TNM Stage and Their Prognostic Significance for Surgically-treated Esophageal Squamous Cell Carcinoma.

BACKGROUND/AIM: The TNM staging system for esophageal cancer is designed to predict survival based on pathological stage in patients who have been treated with surgery alone. However, pathological stage can vary considerably after neoadjuvant therapy due to tumor responses. PATIENTS AND METHODS: We reviewed 110 patients with esophageal squamous cell carcinoma (ESCC) who underwent neoadjuvant chemoradiotherapy (nCRT) followed by surgery, and investigated the effects of nCRT on TNM stage and its prognostic significance. RESULTS: A comparison of pre-treatment clinical and pathological stages (cStage and ypStage, respectively) resulted in 75 (68%) of the patients being down-staged. Good responders (over two-thirds of the primary tumor reduced by nCRT) comprised 100%, 83%, 69%, 52% and 50% of patients with ypStages 0, I, II, III and IV, respectively (p=0.001). In addition, 62 (83%) and 20 (57%) of patients with and without down-staged tumors, respectively, were pathological good responders (p=0.004). We found that cStage did not significantly correlate with survival, whereas univariate analysis significantly associated ypStages III/IV (p=0.003) and down-staged tumors (p=0.04) with overall survival (OS). Multivariate analysis selected ypStage III/IV (HR=3.26; 95% CI=1.52-6.99; p=0.002) and no down-staging (HR=2.06; 95%CI=1.16-3.64, p=0.01) as independent covariates for OS. CONCLUSION: nCRT could lead to down-staged ESCC tumors for many patients and a good prognosis. The correlation between ypStage and pathological response to nCRT indicated that ypStage could stratify survival and serve as a prognostic predictor after trimodal therapy.

Ability of Fluorine-18 Fluorodeoxyglucose Positron Emission Tomography to Predict Outcomes of Neoadjuvant Chemoradiotherapy Followed by Surgical Treatment for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Responses of esophageal cancer to neoadjuvant therapy and patient prognosis are difficult to predict preoperatively. This study aimed to determine the ability of fluorine-18 fluorodeoxyglucose ((18)FDG) positron emission tomography (FDG-PET) to predict outcomes of trimodal therapy on esophageal squamous cell carcinoma (ESCC). METHODS: The responses of 111 patients with ESCC were monitored using FDG-PET before and after neoadjuvant chemoradiotherapy (nCRT) followed by surgical treatment. Associations between the maximum standardized uptake value (SUVmax) and pathologic responses (PRs) and prognosis were analyzed. RESULTS: Responses were significantly associated with SUVmax after nCRT (post-SUVmax) and with the rate of decreases in the SUVmax (%ΔSUVmax) of the primary tumor. The optimal cutoffs for post-SUVmax and %ΔSUVmax determined from receiver operating characteristic (ROC) curves were 2.7 (area under the curve [AUC], 0.68; 95% confidence interval [CI], 0.58-0.78; p = 0.001) and 75 (AUC, 0.64; 95% CI, 0.54-0.75; p = 0.01) for predicting a pathologic complete response (pCR) and 3.7 (AUC, 0.76; 95% CI, 0.63-0.89; p < 0.001) and 70 (AUC, 0.65; 95% CI, 0.52-0.78; p = 0.02) for predicting a good response according to Japan Esophageal Society response criteria. These values reliably separated patients into groups with and without pCR and with and without a good response. Multivariate analysis showed that %ΔSUVmax (≤70 and >70) was an independent prognostic factor for disease-specific survival (hazard ratio [HR], 0.45; 95% CI, 0.21-0.98; p = 0.04). CONCLUSIONS: SUVmax is a valuable preoperative predictor of tumor response and survival among patients who undergo trimodal therapy for ESCC.

[A clinical study of endoscopic local coagulation therapy for hepatocellular carcinoma (HCC)].

Eighteen subjects with cases of HCC who underwent endoscopic local coagulation therapy at Hiroshima City Hospital between 1998 and 2004 were studied and compared with 6 cases of HCC patients who underwent laparoscopic partial hepatectomy during the same period. The subjects composed of 10 cases of laparoscopic microwave coagulation therapy (L-MCT), 5 cases of laparoscopic radio frequency ablation therapy (L-RFA), and 3 cases of thoracoscopic microwave coagulation therapy (T-MCT). The operation time was 114 minutes for L-MCT and 92 minutes for L-RFA, both of which were significantly shorter than 208 minutes for resection cases. No complications were developed in any of the cases and the postoperative hospitalization period of the cases was 13.1 days, 8.2 days, and 13.0 days, respectively. Although each case of local recurrence was observed both in L-MCT and L-RFA groups, one case displayed observation difficulty from the liver surface and the other required a daughter nodule. The three-year survival rate was 71.4%, while the five-year survival rate was 53.6%. Endoscopic local coagulation therapy is not too invasive and useful for hepatocellular carcinoma in which percutaneous RFA is difficult. However, it is well indicated when the scope is evident with observation being feasible from the liver surface.